Hormone Therapy Can Increase Bone Mass, New Study Says

By JANE E. BRODY

Published: November 6, 1996

Hormone replacement therapy can do more than slow the loss of bone after menopause; it can actually increase bone mass even in women who start using it in their 60's, a new study has shown.

The study, which had already shown improvements in cholesterol levels in women taking postmenopausal hormones, has now demonstrated an increase in bone density of the spine and hip during the first three years of replacement therapy.

Women who take no hormones after menopause experience a rapid loss of bone density lasting several years. If the hormone-induced increase in bone mass is maintained over the years, it would be expected to significantly reduce the risk of osteoporosis and resulting vertebral and hip fractures as the women age. Currently 1 in 5 white women past 50 has osteoporosis in both the hip and spine. An estimated 15 percent of postmenopausal women will fracture a hip and 25 percent to 40 percent will suffer spine-shortening and often painful vertebral fractures.

The new finding, from a large government-financed trial called PEPI (for Postmenopausal Estrogen/Progestin Interventions), is reported in today's issue of The Journal of the American Medical Association. The study, conducted at seven clinical centers among 875 healthy women aged 45 to 64, is sponsored by the National Heart, Lung and Blood Institute.

But another study in the journal suggests that with or without hormone replacement, preserving women's bones as they age may come at a price: an increased risk of developing breast cancer after age 65. This finding may reflect the effects of higher levels of natural estrogens, as well as any hormones the women might take.

The PEPI study assessed the short-term health effects of four hormone replacement regimens: conjugated equine estrogens (Premarin) alone or in sequence with medroxyprogesterone acetate (Provera), the two hormones taken together continuously and the estrogens given in sequence with a micronized progesterone isolated from soybeans.

No difference in the effects on bone were noted for the four regimens among those women who continued to use the randomly assigned therapy throughout the study period. However, women on the sequential regimens were more likely to drop out of the study, usually because it resulted in menstrual-like monthly bleeding which they found objectionable.

Over three years, participants who took a look-alike placebo lost on average 2.8 percent of spinal bone density and 2.2 percent of the density of their hip bones, while those who stayed on hormone therapy gained an average of 5.1 percent spinal bone density and 2.3 percent hip bone density.

The PEPI study findings corroborate those of another large study of a different hormone combination, also published today in the journal. The second study, called CHART (for Continuous Hormones as Replacement Therapy), examined the postmenopausal effects on bone density of the hormones commonly used in oral contraceptives. It showed that women who took a combination of the estrogen ethinyl estradiol and the progestational agent norethindrone acetate experienced a dose-related increase in bone mineral density over two years. Bone density did not improve significantly in those who took just the estrogen component, although estrogen users were far less likely to lose bone after menopause than were women who took no hormones.

Estrogen without a progestational agent is no longer recommended for women who still have a uterus, since unopposed estrogen can stimulate the growth of the uterine lining and increase a woman's risk of developing endometrial cancer.

The study that found a relationship between strong bones and breast cancer, called the Study of Osteoporotic Fractures, was not designed to examine the effects of hormone replacement. Nor was it intended to measure the relationship between bone mass and breast cancer, so its findings are at best provocative and suggestive, not conclusive.

It has long been known that breast tissue grows in response to estrogen, although studies examining the influence of postmenopausal estrogens on breast cancer risk have produced conflicting findings. The amount of estrogen used in hormone replacement is much lower than that produced by women's ovaries before menopause. The researchers, headed by Dr. Jane A. Cauley, an epidemiologist at the University of Pittsburgh, said they hoped their observation would lead to a better understanding of the causes of osteoporosis and breast cancer and improved methods of prevention.

Dr. Cauley and her colleagues at four medical centers studied nearly 7,000 women for an average of three years. They found that women with the greatest bone density in their hips, spines and wrists also had the highest incidence of breast cancer -- two to two and one-half times greater than women with the least dense bones. A previous 12-year study of women who had suffered wrist fractures had revealed a surprisingly low rate of breast cancer.

Dr. Cauley and colleagues suggested that the difference in breast cancer risk could reflect the stimulating effects on both bone and breast tissue of estrogens produced in the body or taken as therapy or both. It may also result from differences in other hormones, especially insulin, which can affect both bone and breast tissue, the researchers wrote.

In an editorial accompanying the new reports, Dr. Janet Henrich and her colleagues at the Yale University School of Medicine in New Haven suggested that as scientists continue to unravel the sensitivity of different tissue to different forms of estrogen, it may lead to hormonal therapies that would enhance bone and reduce heart disease without increasing cancer risk.